This includes Ataxia-telegiectasia, Chédiak-Higashi syndrome, DiGeorge syndrome, Griscelli syndrome and Marinesco-Sjogren syndrome.

The diagnostic work up usually includes and MRI of the brain, an EEG, ophthalmic examination and a cardiac ECHO.

Muscle biopsy - which is not commonly done - may show storage of abnormal material and secondary mitochondrial abnormalities in skeletal muscle. Other features that may be seen on muscle biopsy include variability in fibre size, increase in internal and centralized nuclei, type 1 fibre hypotrophy with normally sized type 2 fibres, increased glycogen storage and variable vacuoles on light microscopy

The diagnosis is confirmed by sequencing of the EPG5.

Genetic testing may be available for mutations in the FGDY1 gene. Genetic counseling is indicated for individuals or families who may carry this condition, as there are overlapping features with fetal alcohol syndrome.

Other examinations or tests can help with diagnosis. These can include:

detailed family history

- conducting a detailed physical examination to document morphological features

- testing for genetic defect in FGDY1

- x-rays can identify skeletal abnormalities

- echo cardiogram can screen for heart abnormalities

- CT scan of the brain for cystic development

- X-ray of the teeth

- Ultrasound of abdomen to identify undescended testis

Differential diagnosis includes Angelman syndrome, Mowat–Wilson syndrome and Rett syndrome.

Diagnosis is based on the distinctive cry and accompanying physical problems. These common symptoms are quite easily observed in infants. Affected children are typically diagnosed by a doctor or nurse at birth. Genetic counseling and genetic testing may be offered to families with individuals who have cri du chat syndrome. Prenatally the deletion of the cri du chat related region in the p arm of chromosome 5 can be detected from amniotic fluid or chorionic villi samples with BACs-on-Beads technology. G-banded karyotype of a carrier is also useful. Children may be treated by speech, physical and occupational therapists. Heart abnormalities often require surgical correction.

Though the outcome for individuals with either form of the tetrasomy is highly variable, mosaic individuals consistently experience a more favourable outcome than those with the non-mosaic form. Some affected infants die shortly after birth, particularly those with the non-mosaic tetrasomy. Many patients do not survive to reproductive age, while others are able to function relatively normally in a school or workplace setting. Early diagnosis and intervention has been shown to have a strong positive influence on the prognosis.

1. Clinical Genetics and Genetic Testing

Genetic testing is necessary to confirm the diagnosis of PMS. A prototypical terminal deletion of 22q13 can be uncovered by karyotype analysis, but many terminal and interstitial deletions are too small to detect with this method. Chromosomal microarray should be ordered in children with suspected developmental delays or ASD. Most cases will be identified by microarray; however, small variations in genes might be missed. The falling cost for whole exome sequencing may replace DNA microarray technology for candidate gene evaluation. Biological parents should be tested with fluorescence "in situ" hybridization (FISH) to rule out balanced translocations or inversions. Balanced translocation in a parent increases the risk for recurrence and heritability within families (figure 3).

Clinical genetic evaluations and dysmorphology exams should be done to evaluate growth, pubertal development, dysmorphic features (table 1) and screen for organ defects (table 2)

2. Cognitive and Behavioral Assessment

All patients should undergo comprehensive developmental, cognitive and behavioral assessments by clinicians with experience in developmental disorders. Cognitive evaluation should be tailored for individuals with significant language and developmental delays. All patients should be referred for specialized speech/language, occupational and physical therapy evaluations.

3. Neurological Management

Individuals with PMS should be followed by a pediatric neurologist regularly to monitor motor development, coordination and gait, as well as conditions that might be associated with hypotonia. Head circumference should be performed routinely up until 36 months. Given the high rate of seizure disorders (up to 41% of patients) reported in the literature in patients with PMS and its overall negative impact on development, an overnight video EEG should be considered early to rule out seizure activity. In addition, a baseline structural brain MRI should be considered to rule out the presence of structural abnormalities.

4. Nephrology

All patients should have a baseline renal and bladder ultrasonography and a voiding cystourethrogram should be considered to rule out structural and functional abnormalities. Renal abnormalities are reported in up to 38% of patients with PMS. Vesicouretral reflux, hydronephrosis, renal agenesis, dysplasic kidney, polycystic kidney and recurrent urinary tract infections have all been reported in patients with PMS.

5. Cardiology

Congenital heart defects (CHD) are reported in samples of children with PMS with varying frequency (up to 25%)(29,36). The most common CHD include tricuspid valve regurgitation, atrial septal defects and patent ductus arteriousus. Cardiac evaluation, including echocardiography and electrocardiogram, should be considered.

6. Gastroenterology

Gastrointestinal symptoms are common in individuals with PMS. Gastroesophageal reflux, constipation, diarrhea and cyclic vomiting are frequently described.

Table 3: Clinical Assessment Recommendations in Phelan McDermid Syndrome.

Diagnosis is made by showing a mutation in the TCF4 gene.

Around 50% of those affected show abnormalities on brain imaging. These include hypoplastic corpus callosum with a missing rostrum and posterior part of the splenium with bulbous caudate nuclei bulging towards the frontal horns.

Electroencephalograms show an excess of slow components.

All have low levels of immunoglobulin M (IgM) but features of an immunodeficiency are absent.

Diagnosing Jacobsen Syndrome can be difficult in some cases because it is a rare chromosomal disorder. There are a variety of tests that can be carried out like karyotype, cardiac echocardiogram, a renal sonogram, a platelet count, blood count, a brain imaging study. Genetic testing can be carried out for diagnosis. In which chromosomes are stained to give a barcode like appearance and studied under the microscope which reveals the broken and deleted genes. It can also be diagnosed early in the prenatal stage if there are any abnormalities seen in the ultrasound. A simple assessment of the symptoms can be done to diagnose the Syndrome. A thorough physical examination could be carried out to assess the symptoms.

13q deletion syndrome can only be definitively diagnosed by genetic analysis, which can be done prenatally or after birth. Increased nuchal translucency in a first-trimester ultrasound may indicate the presence of 13q deletion.

Potocki–Shaffer syndrome can be detected through array comparative genomic hybridization (aCGH).

Some symptoms can be managed with drug therapy, surgery and rehabilitation, genetic counselling, and palliative care.

Since tetrasomy 9p is not usually inherited, the risk of a couple having a second child with the disorder is minimal. While patients often do not survive to reproductive age, those who do may or may not be fertile. The risk of a patient's child inheriting the disorder is largely dependent on the details of the individual's case.

The diagnosis of Wilson–Turner syndrome is based upon a clinical evaluation, a detailed patient history, and identification of characteristic features. Molecular genetic testing for mutations in the HDAC8 gene is now available to confirm the diagnosis.

Even though clinical diagnostic criteria have not been 100 percent defined for genitopatellar syndrome, the researchers stated that the certain physical features could relate to KAT6B mutation and result in the molecular genetic testing. The researchers stated that the Individuals with two major features or one major feature and two minor features are likely to have a KAT6B mutation.

To diagnose the Genitopatellar Syndrome, there are multiple ways to evaluate.

Medical genetics consultation

- Evaluation by developmental specialist

- Feeding evaluation

- Baseline hearing evaluation

- Thyroid function tests

- Evaluation of males for cryptorchidism

- Orthopedic evaluation if contractures are present or feet/ankles are malpositioned

- Hip radiographs to evaluate for femoral head dislocation

- Renal ultrasound examination for hydronephrosis and cysts

- Echocardiogram for congenital heart defects

- Evaluation for laryngomalacia if respiratory issues are present

- Evaluation by gastroenterologist as needed, particularly if bowel malrotation is suspected

The Wilson–Turner syndrome is characterized by mild to moderate range of intellectual disability, obesity, tapered fingers, and mood swings. Males also suffer from gynecomastia and hypogonadism. In order to be diagnosed with Wilson-Turner Syndrome, male patients must suffer from intellectual disability, obesity, and gynecomastia. Females do not necessarily have to have noticeable phenotype but can be diagnosed with this disorder by studying her family history and identifying others with the disorder. It has been noted that children with Wilson-Turner Syndrome will display speech development delay and excessive drooling. Males can be confirmed by testing androgen levels. Female carriers will show silencing of the gene a complex X inactivation.

Emanuel Syndrome can be diagnosed with a karyotype, with FISH, or with a chromosomal microarray analysis. .

The diagnosis of Jackson–Weiss syndrome is done via the following:

- Genetic testing

- Clinical presentation

Emanuel Syndrome does not have a cure, but individual symptoms may be treated. Assessments of individual systems, such as the cardiovascular, gastrointestinal, orthopedic, and neurological may be necessary to determine the extent of impairment and options for treatment.

The DDx for this condition includes metopic synostosis, as well as Lambdoida synostosis.

Though only definitively diagnosable by genetic sequence testing, including a G band analysis, ATR-16 syndrome may be diagnosed from its constellation of symptoms. It must be distinguished from ATR-X syndrome, a very similar disease caused by a mutation on the X chromosome, and cases of alpha-thalassemia that co-occur with intellectual disabilities with no underlying genetic relationship.

It is traditionally characterized by hypotonia, short stature, hyperphagia, obesity, behavioral issues (specifically OCD-like behaviors), small hands and feet, hypogonadism, and mild intellectual disability. However, with early diagnosis and early treatment (such as with growth hormone therapy), the prognosis for persons with PWS is beginning to change. Like autism, PWS is a spectrum disorder and symptoms can range from mild to severe and may change throughout the person's lifetime. Various organ systems are affected.

Traditionally, Prader–Willi syndrome was diagnosed by clinical presentation. Currently, the syndrome is diagnosed through genetic testing; testing is recommended for newborns with pronounced hypotonia. Early diagnosis of PWS allows for early intervention as well as the early prescription of growth hormone. Daily recombinant growth hormone (GH) injections are indicated for children with PWS. GH supports linear growth and increased muscle mass, and may lessen food preoccupation and weight gain.

The mainstay of diagnosis is genetic testing, specifically DNA-based methylation testing to detect the absence of the paternally contributed Prader–Willi syndrome/Angelman syndrome (PWS/AS) region on chromosome 15q11-q13. Such testing detects over 97% of cases. Methylation-specific testing is important to confirm the diagnosis of PWS in all individuals, but especially those who are too young to manifest sufficient features to make the diagnosis on clinical grounds or in those individuals who have atypical findings.

Prader–Willi syndrome is often misdiagnosed as other syndromes due to many in the medical community's unfamiliarity with PWS. Sometimes it is misdiagnosed as Down syndrome, simply because of the relative frequency of Down syndrome compared to PWS.

Treatments for ATR-16 syndrome depend on the symptoms experienced by any individual. Alpha thalassemia is usually self-limiting, but in some cases may require a blood transfusion or chelating treatment.

Some people may have some mental slowness, but children with this condition often have good social skills. Some males may have problems with fertility.

The diagnosis of the disease is mainly clinical (see diagnostic criteria). A laboratory workup is needed primarily to investigate for the presence of associated disorders (metabolic, autoimmune, and renal diseases).

- Every patient should have a fasting blood glucose and lipid profile, creatinine evaluation, and urinalysis for protein content at the first visit, after which he/she should have these tests on a regular basis.

- Although uncommon, lipid abnormalities can occur in the form of raised triglyceride levels and low high-density lipoprotein cholesterol levels.

- Patients usually have decreased serum C3 levels, normal levels of C1 and C4, and high levels of C3NeF (autoantibody), which may indicate the presence of renal involvement.

- Antinuclear antibodies (ANA) and antidouble-stranded deoxyribonucleic acid (DNA) antibodies have reportedly been observed in some patients with acquired partial lipodystrophy.

- A genetic workup should be performed if the familial form of lipodystrophy is suggested.

Laboratory work for associated diseases includes:

- Metabolic disease - fasting glucose, glucose tolerance test, lipid profile, and fasting insulin to characterize the insulin resistance state; free testosterone (in women) to look for polycystic ovary syndrome.

- Autoimmune disease - ANA, antidouble-stranded DNA, rheumatoid factor, thyroid antibodies, C3, and C3NeF.

As a confirmatory test, whole-body MRI usually clearly demonstrates the extent of lipodystrophy. MRI is not recommended on a routine basis.

There is no cure for this syndrome. Treatment is supportive and symptomatic. All children with Mowat–Wilson syndrome required early intervention with speech therapy, occupational therapy and physical therapy.